Solvent-Free Enantioselective Friedländer Condensation with Wet 1,1′-Binaphthalene-2,2′-diamine-Derived Prolinamides as Organocatalysts

• Published in: The Journal of Organic Chemistry
• Main Authors: Bañón Caballero, Abraham, Guillena, Gabriela, Nájera, Carmen
• Other Authors: Universidad de Alicante. Departamento de Química Orgánica, Universidad de Alicante. Instituto Universitario de Síntesis Orgánica, Catálisis Estereoselectiva en Síntesis Orgánica (CESO), Síntesis Asimétrica (SINTAS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Chemical Society 2013
• Subjects: Solvent-free; Enantioselective; Friedländer condensation; Wet 1,1′-binaphthalene-2,2′-diamine-derived prolinamides; Organocatalysis; Química Orgánica; Orca
• Online Access: http://hdl.handle.net/10045/38257; https://doi.org/10.1021/jo400522m

Wet unsupported and supported 1,1′-binaphthalene-2,2′-diamine (BINAM) derived prolinamides are efficient organocatalysts under solvent-free conditions at room temperature to perform the synthesis of chiral tacrine analogues in good yields (up to 93%) and excellent enantioselectivies (up to 96%). The Friedländer reaction involved in this process takes place with several cyclohexanone derivatives and 2-aminoaromatic aldehydes, and it is compatible with the presence of either electron-withdrawing or electron-donating groups at the aromatic ring of the 2-aminoaryl aldehyde derivatives used as electrophiles. The reaction can be extended to cyclopentanone derivatives, affording a regioisomeric but separable mixture of products. The use of the wet silica gel supported organocatalyst, under solvent-free conditions, for this process led to the expected product (up to 87% enantiomeric excess), with its reuse being possible at least up to five times. This work was financially supported by the Ministerio de Ciencia e Innovación (MICINN: Projects: CTQ2010-20387 and Consolider Ingenio 2010 CSD2007-00006), the Generalitat Valenciana (Prometeo/2009/039, the University of Alicante and the EU (ORCA action CM0905). A.B.-C. thanks the Spanish MICINN for a predoctoral fellowship (FPU AP2009-3601).